FAM19A4/miR124-2 methylation in invasive cervical cancer: A retrospective cross-sectional worldwide study

Frederique J Vink, Chris J L M Meijer, Gary M Clifford, Mario Poljak, Anja Oštrbenk, Karl Ulrich Petry, Beate Rothe, Jesper Bonde, Helle Pedersen, Silvia de Sanjosé, Montserrat Torres, Marta Del Pino, Wim G V Quint, Kate Cuschieri, Elia Alcañiz Boada, Nienke E van Trommel, Birgit I Lissenberg-Witte, Arno N Floore, Albertus T Hesselink, Renske D M Steenbergen & 2 others Maaike C G Bleeker, Daniëlle A M Heideman

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In this study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7 - 99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusE-pub ahead of print - 7 Aug 2019

Cite this

Vink, Frederique J ; Meijer, Chris J L M ; Clifford, Gary M ; Poljak, Mario ; Oštrbenk, Anja ; Petry, Karl Ulrich ; Rothe, Beate ; Bonde, Jesper ; Pedersen, Helle ; de Sanjosé, Silvia ; Torres, Montserrat ; Del Pino, Marta ; Quint, Wim G V ; Cuschieri, Kate ; Alcañiz Boada, Elia ; van Trommel, Nienke E ; Lissenberg-Witte, Birgit I ; Floore, Arno N ; Hesselink, Albertus T ; Steenbergen, Renske D M ; Bleeker, Maaike C G ; Heideman, Daniëlle A M. / FAM19A4/miR124-2 methylation in invasive cervical cancer : A retrospective cross-sectional worldwide study. In: International Journal of Cancer. 2019.
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title = "FAM19A4/miR124-2 methylation in invasive cervical cancer: A retrospective cross-sectional worldwide study",
abstract = "Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In this study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation specific PCR (qMSP)-based assay (QIAsure Methylation Test{\circledR}). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3{\%}; 95{\%} CI: 96.7 - 99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. This article is protected by copyright. All rights reserved.",
author = "Vink, {Frederique J} and Meijer, {Chris J L M} and Clifford, {Gary M} and Mario Poljak and Anja Oštrbenk and Petry, {Karl Ulrich} and Beate Rothe and Jesper Bonde and Helle Pedersen and {de Sanjos{\'e}}, Silvia and Montserrat Torres and {Del Pino}, Marta and Quint, {Wim G V} and Kate Cuschieri and {Alca{\~n}iz Boada}, Elia and {van Trommel}, {Nienke E} and Lissenberg-Witte, {Birgit I} and Floore, {Arno N} and Hesselink, {Albertus T} and Steenbergen, {Renske D M} and Bleeker, {Maaike C G} and Heideman, {Dani{\"e}lle A M}",
note = "This article is protected by copyright. All rights reserved.",
year = "2019",
month = "8",
day = "7",
doi = "10.1002/ijc.32614",
language = "English",
journal = "International Journal of Cancer",
issn = "0020-7136",
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Vink, FJ, Meijer, CJLM, Clifford, GM, Poljak, M, Oštrbenk, A, Petry, KU, Rothe, B, Bonde, J, Pedersen, H, de Sanjosé, S, Torres, M, Del Pino, M, Quint, WGV, Cuschieri, K, Alcañiz Boada, E, van Trommel, NE, Lissenberg-Witte, BI, Floore, AN, Hesselink, AT, Steenbergen, RDM, Bleeker, MCG & Heideman, DAM 2019, 'FAM19A4/miR124-2 methylation in invasive cervical cancer: A retrospective cross-sectional worldwide study' International Journal of Cancer. https://doi.org/10.1002/ijc.32614

FAM19A4/miR124-2 methylation in invasive cervical cancer : A retrospective cross-sectional worldwide study. / Vink, Frederique J; Meijer, Chris J L M; Clifford, Gary M; Poljak, Mario; Oštrbenk, Anja; Petry, Karl Ulrich; Rothe, Beate; Bonde, Jesper; Pedersen, Helle; de Sanjosé, Silvia; Torres, Montserrat; Del Pino, Marta; Quint, Wim G V; Cuschieri, Kate; Alcañiz Boada, Elia; van Trommel, Nienke E; Lissenberg-Witte, Birgit I; Floore, Arno N; Hesselink, Albertus T; Steenbergen, Renske D M; Bleeker, Maaike C G; Heideman, Daniëlle A M.

In: International Journal of Cancer, 07.08.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - FAM19A4/miR124-2 methylation in invasive cervical cancer

T2 - A retrospective cross-sectional worldwide study

AU - Vink, Frederique J

AU - Meijer, Chris J L M

AU - Clifford, Gary M

AU - Poljak, Mario

AU - Oštrbenk, Anja

AU - Petry, Karl Ulrich

AU - Rothe, Beate

AU - Bonde, Jesper

AU - Pedersen, Helle

AU - de Sanjosé, Silvia

AU - Torres, Montserrat

AU - Del Pino, Marta

AU - Quint, Wim G V

AU - Cuschieri, Kate

AU - Alcañiz Boada, Elia

AU - van Trommel, Nienke E

AU - Lissenberg-Witte, Birgit I

AU - Floore, Arno N

AU - Hesselink, Albertus T

AU - Steenbergen, Renske D M

AU - Bleeker, Maaike C G

AU - Heideman, Daniëlle A M

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/8/7

Y1 - 2019/8/7

N2 - Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In this study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7 - 99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. This article is protected by copyright. All rights reserved.

AB - Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In this study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7 - 99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. This article is protected by copyright. All rights reserved.

U2 - 10.1002/ijc.32614

DO - 10.1002/ijc.32614

M3 - Article

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

ER -